Mutational analysis of cervical cytology improves diagnosis of endometrial cancer: A prospective multicentre cohort study.
diagnosis
endometrial neoplasms
high-throughput nucleotide sequencing
molecular pathology
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
16
06
2019
revised:
16
08
2019
accepted:
30
08
2019
pubmed:
17
9
2019
medline:
1
7
2020
entrez:
17
9
2019
Statut:
ppublish
Résumé
Endometrial carcinoma (EC) is traditionally diagnosed by a histopathological assessment of an endometrial biopsy, leaving up to 30% of patients undiagnosed due to technical failure or an inadequate amount of tissue. The aim of the current study is to assess whether mutational analysis of cervical cytology or pipelle endometrial biopsies improves the diagnostic accuracy of traditional histopathological diagnosis of EC. This prospective multicentre cohort study included patients surgically treated for EC or a benign gynaecological condition (control group). A Pap brush sample, cervicovaginal self-sample, pipelle endometrial biopsy and surgical specimen of either the EC or normal endometrium were obtained. A targeted next-generation sequencing panel was used to analyse these samples for mutations in eight genes. Sensitivity, specificity and predictive values were calculated. Fifty-nine EC patients and 31 control patients were included. In these patients, traditional histopathological diagnosis by pipelle had a sensitivity of 79% and a specificity of 100%. For EC patients, 97% of surgical specimens contained at least one mutation. Mutational analysis of Pap brush samples, self-samples and pipelle endometrial biopsies yielded a sensitivity of 78, 67 and 96% with a specificity of 97, 97 and 94%, respectively. Combining one of these three methods with histopathological pipelle endometrial biopsy evaluations yielded a sensitivity of 96, 93 and 96%, respectively. Our study has shown that mutational analysis of either cervical cytology or pipelle endometrial biopsies improves diagnosis of EC. Prospective validation will support implementation in clinical practice.
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2628-2635Informations de copyright
© 2019 UICC.
Références
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
ACOG Committee Opinion No. 734. The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding. Obstet Gynecol 2018;131:e124-9.
Seamark CJ. Endometrial sampling in general practice. Br J Gen Pract 1998;48:1597-8.
Rezk M, Dawood R, Masood A. The safety and acceptability of Pipelle endometrial sampling in premenopausal women in comparison to postmenopausal women with abnormal uterine bleeding. Minerva Ginecol 2016;68:492-6.
van Hanegem N, Breijer MC, Slockers SA, et al. Diagnostic workup for postmenopausal bleeding: a randomised controlled trial. BJOG 2017;124:231-40.
Visser NCM, Reijnen C, Massuger L, et al. Accuracy of endometrial sampling in endometrial carcinoma: a systematic review and meta-analysis. Obstet Gynecol 2017;130:803-13.
Clark TJ, Mann CH, Shah N, et al. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review. BJOG 2002;109:313-21.
Van Doorn HC, Timmermans A, Opmeer BC, et al. What is the recurrence rate of postmenopausal bleeding in women who have a thin endometrium during a first episode of postmenopausal bleeding? Acta Obstet Gynecol Scand 2008;87:89-93.
Lindor NM, Petersen GM, Hadley DW, et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 2006;296:1507-17.
Kinde I, Bettegowda C, Wang Y, et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med 2013;5:167ra4.
Wang Y, Li L, Douville C, et al. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med 2018;10:eaap8793.
Mota A, Colas E, Garcia-Sanz P, et al. Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers. Mod Pathol 2017;30:134-45.
Eijkelenboom A, Kamping EJ, Kastner-van Raaij AW, et al. Reliable next-generation sequencing of formalin-fixed, paraffin-embedded tissue using single molecule tags. J Mol Diagn 2016;18:851-63.
Visser NC, Breijer MC, Herman MC, et al. Factors attributing to the failure of endometrial sampling in women with postmenopausal bleeding. Acta Obstet Gynecol Scand 2013;92:1216-22.
Hussein YR, Broaddus R, Weigelt B, et al. The genomic heterogeneity of FIGO grade 3 endometrioid carcinoma impacts diagnostic accuracy and reproducibility. Int J Gynecol Pathol 2016;35:16-24.
Thomas S, Hussein Y, Bandyopadhyay S, et al. Interobserver variability in the diagnosis of uterine high-grade Endometrioid carcinoma. Arch Pathol Lab Med 2016;140:836-43.
Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol 2013;37:874-81.
Nair N, Camacho-Vanegas O, Rykunov D, et al. Genomic analysis of uterine lavage fluid detects early endometrial cancers and reveals a prevalent landscape of driver mutations in women without Histopathologic evidence of cancer: a prospective cross-sectional study. PLoS Med 2016;13:e1002206.
Yan WF, Wu G, Sun PC, et al. P53 mutations occur more commonly than KRAS mutations in colorectal adenoma. Int J Clin Exp Med 2015;8:1370-5.
Liau JY, Tsai JH, Huang WC, et al. BRAF and KRAS mutations in tubular apocrine adenoma and papillary eccrine adenoma of the skin. Hum Pathol 2018;73:59-65.
Groesser L, Herschberger E, Landthaler M, et al. FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis. Br J Dermatol 2012;166:784-8.
Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497:67-73.
van der Putten LJM, van Hoof R, Tops BBJ, et al. Molecular profiles of benign and (pre)malignant endometrial lesions. Carcinogenesis 2017;38:329-35.
Matias-Guiu X, Prat J. Molecular pathology of endometrial carcinoma. Histopathology 2013;62:111-23.
Wiegand KC, Lee AF, Al-Agha OM, et al. Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas. J Pathol 2011;224:328-33.
Guan B, Mao TL, Panuganti PK, et al. Mutation and loss of expression of ARID1A in uterine low-grade endometrioid carcinoma. Am J Surg Pathol 2011;35:625-32.
Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000;92:924-30.
Tashiro H, Blazes MS, Wu R, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 1997;57:3935-40.
Oda K, Stokoe D, Taketani Y, et al. High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res 2005;65:10669-73.
Velasco A, Bussaglia E, Pallares J, et al. PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. Hum Pathol 2006;37:1465-72.
Geels YP, van der Putten LJ, van Tilborg AA, et al. Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma arising from atrophic endometrium. Gynecol Oncol 2015;137:245-51.
Geels YP, van der Putten LJM, van Tilborg AAG, et al. Immunohistochemical profiles of endometrioid endometrial carcinomas with and without metastatic disease. Appl Immunohistochem Mol Morphol 2018;26:173-9.
Talhouk A, McConechy MK, Leung S, et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017;123:802-13.
Talhouk A, McConechy MK, Leung S, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 2015;113:299-310.